The transcription factor PAX 5 (BSAP) is essential for commitment of lymphoid progenitors to the B lymphocyte lineage. PAX 5 fulfils a dual role by repressing B lineage ‘inappropriate’ genes and simultaneously activating B lineage-specific genes. This transcriptional reprogramming restricts the broad signaling capacity of uncommitted progenitors to the B cell pathway, regulates cell adhesion and migration, induces V(H)-DJ(H) recombination, facilitates (pre-)B cell receptor signaling and promotes development to the mature B cell stage. Conditional PAX 5 inactivation in early and late B lymphocytes revealed an essential role for PAX 5 in controlling the identity and function of B cells throughout B lymphopoiesis. PAX 5 has also been implicated in human B cell malignancies, as it is deregulated by chromosomal translocations in a subset of acute lymphoblastic leukemias and non-Hodgkin lymphomas.
PAX 5 and Myc are the only 2 transcription factors consistently overexpressed in human follicular lymphoma cells compared with their putative normal counterparts, germinal center B cells (Mikkola I., et al., Blood, 99:282-289, 2002). Similarly, in DLBCLs, MYC and PAX 5 are the only 2 transcription factor-encoding genes with high frequencies of hypermutations (Pasqualucci, L., et al. 2001). Mutations in PAX 5 were also found, albeit with lower frequency, in Burkitt lymphomas with translocated Myc. Importantly, PAX 5 mutations cluster in regulatory sequences surrounding exon 1B, suggestive of its overexpression. Overall, high levels of PAX 5 protein have been reported in almost all non-Hodgkin lymphomas, but in very few acute leukemias (Krenas, L., et. al. 1998). Genetic data also support the involvement of PAX 5 in lymphomagenesis (Mullighan, et al., 2007; Cozma et al., 2007).
Use of anti-PAX 5 immunostaining in the diagnosis of pre-B acute lymphostatic leukemia and classic Hodkin lymphoma versus ALCL of T and “null” cell type was estimated to be very valuable. It was also useful in differential diagnosis between lymphoplasmatic lymphoma and plasmacytoma. Thus, it has been shown that even though there is an excellent correlation between CD20 and PAX 5 expression, anti-PAX 5 immunostaining exceeds the specificity and sensitivity of CD20 immunostaining because of PAX 5 earlier expression in B-cell differentiation and it is possible to detect all committed B cells, including classic Hodgkin lymphoma (Torlakovic E., et al., 2002).